Recherche clinique ville-hôpital, Méthodologies et Société
Présentation
L’équipe 7334 REMES (Recherche Clinique ville-hôpital, Méthodologies et Société) sous la direction du Pr Olivier Chassany a la particularité de regrouper des médecins de ville et des hôpitaux, autour de travaux de recherche clinique qui placent le patient au centre de la prise en charge et des décisions médicales le concernant.
- Le 1er axe de recherche de l’équipe dirigé par le Dr Martin Duracinsky analyse la qualité de vie des personnes en situation de pathologie et mesure leurs perceptions (« Patient-Centered Outcomes ») afin d’améliorer leur parcours de vie avec la maladie. Comment vivent-ils avec cette pathologie ? Supportent-ils les traitements associés ? Comment leur prise en charge pourrait être améliorée, facilitée ?...
- Le 2e axe de recherche est quant à lui destiné à améliorer le parcours de soins du patient avec pour ambition de jeter un pont entre la médecine de ville et l’hôpital. Cet axe est rendu possible par la mobilisation des médecins généralistes universitaires de Paris-Diderot et leur collaboration avec d’autres enseignants-chercheurs exerçant à l’hôpital. Du fait de sa spécificité, cet axe est sous la responsabilité de 2 chercheurs, le Pr Isabelle Mahé du côté hôpital et le Pr Jean-Pierre Aubert pour la ville.
Pour finir, les chercheurs de l’EA 7334 REMES travaillent sur deux autres axes.
- Dans le 3e axe, sous la responsabilité de la juriste Mihaela Matei, ils se demandent comment améliorer la législation qui encadre la recherche clinique, en intégrant la notion d’approche basée sur le risque (« risk-based approach »).
- Le 4e axe, confié à Philippe Lechat, concerne le développement d’outils électroniques d’aide à la prescription. Ce projet comporte notamment une recherche sur l’élaboration et la faisabilité des algorithmes nécessaires à la construction d’un logiciel permettant de vérifier la validité, la cohérence et l’adéquation d’une ordonnance médicale des médicaments prescrits pour un patient donné dans une indication thérapeutique définie.
Thèmes de recherche
Axe Patient-Centered Outcomes
Responsable : Dr Martin Duracinsky (duracinsky.m@gmail.com)
Axe Recherche clinique Ville-Hôpital
Responsables : Pr Isabelle Mahé (Isabelle.Mahe@lmr.aphp.fr) & Pr jean Pierre Aubert (docteur.aubert@gmail.com)
Axe Législation et recherche clinique
Responsable : Mihaela Matei
Axe Outils électroniques d’aide à la prescription
Responsable : Pr Philippe Lechat (philippe.lechat@drc.aphp.fr)
[hal-02342800] Noradrenergic neuronal development is impaired by mutation of the proneural HASH-1 gene in congenital central hypoventilation syndrome (Ondine's curse)
Date: 1 Nov 2019 - 12:45
Desc: Congenital central hypoventilation syndrome (CCHS, Ondine's curse) is a rare disorder of the chemical control of breathing. It is frequently associated with a broad spectrum of dysautonomic symptoms, suggesting the involvement of genes widely expressed in the autonomic nervous system. In particular, the HASH-1-PHOX2A-PHOX2B developmental cascade was proposed as a candidate pathway because it controls the development of neurons with a definitive or transient noradrenergic phenotype, upstream from the RET receptor tyrosine kinase and tyrosine hydroxylase. We recently showed that PHOX2B is the major CCHS locus, whose mutation accounts for 60% of cases. We also studied the proneural HASH-1 gene and identified a heterozygous nucleotide substitution in three CCHS patients. To analyze the functional consequences of HASH-1 mutations, we developed an in vitro model of noradrenergic differentiation in neuronal progenitors derived from the mouse vagal neural crest, reproducing in vitro the HASH-PHOX-RET pathway. All HASH-1 mutant alleles impaired noradrenergic neuronal development, when overexpressed from adenoviral constructs. Thus, HASH-1 mutations may contribute to the CCHS phenotype in rare cases, consistent with the view that the abnormal chemical control of breathing observed in CCHS patients is due to the impairment of noradrenergic neurons during early steps of brainstem development.
[hal-03703930] Sleep Disturbance and Total Sleep Time in Persons Living with HIV: A Cross-Sectional Study
Date: 24 Jun 2022 - 15:12
Desc: [...]
[pasteur-02294649] An IgG-induced neutrophil activation pathway contributes to human drug-induced anaphylaxis
Date: 23 Sep 2019 - 16:59
Desc: Anaphylaxis is a systemic acute hypersensitivity reaction that is considered to depend on allergen-specific immunoglobulin E (IgE) antibodies and histamine release by mast cells and basophils. Nevertheless, allergen-specific IgG antibodies have been proposed to contribute when the allergen is an abundant circulating large molecule, e.g., after infusions of therapeutic antibodies or dextran. Data from animal models demonstrate a pathway involving platelet-activating factor (PAF) release by monocytes/macrophages and neutrophils activated via their Fc gamma receptors (FcγRs). We hypothesized that such a pathway may also apply to small drugs and could be responsible for non-IgE-mediated anaphylaxis and influence anaphylaxis severity in humans. We prospectively conducted a multicentric study of 86 patients with suspected anaphylaxis to neuromuscular-blocking agents (NMBAs) during general anesthesia and 86 matched controls. We found that concentrations of anti-NMBA IgG and markers of FcγR activation, PAF release, and neutrophil activation correlated with anaphylaxis severity. Neutrophils underwent degranulation and NETosis early after anaphylaxis onset, and plasma-purified anti-NMBA IgG triggered neutrophil activation ex vivo in the presence of NMBA. Neutrophil activation could also be observed in patients lacking evidence of classical IgE-dependent anaphylaxis. This study supports the existence of an IgG-neutrophil pathway in human NMBA-induced anaphylaxis, which may aggravate anaphylaxis in combination with the IgE pathway or underlie anaphylaxis in the absence of specific IgE. These results reconcile clinical and experimental data on the role of antibody classes in anaphylaxis and could inform diagnostic approaches to NMBA-induced acute hypersensitivity reactions.
[hal-01740290] Four-days-a-week antiretroviral maintenance therapy in virologically controlled HIV-1-infected adults: the ANRS 162-4D trial
Date: 21 Mar 2018 - 17:50
Desc: Background: Intermittent treatment could improve the convenience, tolerability and cost of ART, as well as patients' quality of life. We conducted a 48 week multicentre study of a 4-days-a-week antiretroviral regimen in adults with controlled HIV-1-RNA plasma viral load (VL). Methods: Eligible patients were adults with VL < 50 copies/mL for at least 1 year on triple therapy with a ritonavir-boosted PI (PI/r) or an NNRTI. The study protocol consisted of the same regimen taken on four consecutive days per week followed by a 3 day drug interruption. The primary outcome was the proportion of participants remaining in the strategy with VL < 50 copies/mL up to week 48. The study was designed to show an observed success rate of > 90%, with a power of 87% and a 5% type 1 error. The study was registered with ClinicalTrials.gov (NCT02157311) and EudraCT (2014-000146-29). Results: One hundred patients (82 men), median age 47 years (IQR 40-53), were included. They had been receiving ART for a median of 5.1 (IQR 2.9-9.3) years and had a median CD4 cell count of 665 (IQR 543-829) cells/mm3. The ongoing regimen included PI/r in 29 cases and NNRTI in 71 cases. At 48 weeks, 96% of participants (95% CI 90%-98%) had no failure while remaining on the 4-days-a-week regimen. Virological failure occurred in three participants, who all resumed daily treatment and became resuppressed. One participant stopped the strategy. No severe treatment-related events occurred. Conclusions: Antiretroviral maintenance therapy 4 days a week was effective for 48 weeks in 96% of patients, leading to potential reduction of long-term toxicities, high adherence to the antiretroviral regimen and drug cost saving.
